Peculiarities of Hemostasis and Proteomics in Patients With Acute Myocardial Infarction and Healthy Volunteers After SARS-CоV-2 Infection.

AIM: To identify the features of plasma, platelet hemostasis, and proteomic composition of the blood plasma in patients with acute myocardial infarction (AMI) and healthy volunteers after COVID-19. MATERIAL AND METHODS: The study included patients with AMI who have recently had COVID-19 (AMI-post-COVID, n=56) and patients with AMI who have not recently had COVID-19 (AMI-control, n=141). Healthy volunteers constituted the control groups and were also divided into control-post-COVID (n=32) and control-control (n=71) groups. Previous SARS-CoV-2 infection was determined by anti-N IgG in the blood serum, the level of which persists for 6-10 months after the disease. Hemostasis was evaluated by thromboelastometry (on whole blood), thrombodynamics (on platelet-poor plasma), fibrinolysis, impedance aggregometry, and proteomic analysis. RESULTS: The AMI-post-COVID and AMI-control groups had higher values of thrombus growth rate, size and density based on the data of thromboelastometry and thrombodynamics, as well as increased concentrations of the complement system components, proteins regulating the state of the endothelium, and a number of acute-phase and procoagulant proteins compared to the control groups. Furthermore, in the AMI-post-COVID group, compared to the AMI-control group, the thrombus density was lower, and its lysis rates were higher when measured by the thrombodynamics method on platelet-poor plasma, while the platelet aggregation induced by ADP and thrombin was higher. Also, in the control-post-COVID group, compared to the control-control group, the thrombus formation rate was lower, whereas, in contrast, the thrombus size as measured by the thrombodynamics method and the platelet aggregation induced by arachidonic acid and thrombin were higher. In addition, in the AMI-post-COVID group, compared to the AMI-control group, the concentrations of proteins involved in inflammation and hemostasis were lower. CONCLUSION: Patients with AMI who have recently had COVID-19 are characterized by a less pronounced activation of the immune response compared to patients with AMI who have not had COVID-19. This may be due to long-term chronic inflammation and depletion of components of the immune activation system after SARS-CoV-2 infection. Long-term activation of the hemostasis system in both patients with AMI and healthy volunteers after COVID-19 is primarily due to the platelet component of hemostasis.

[Surgical treatment of littoral cell angioma of the spleen]. / Opyt khirurgicheskogo lecheniya «pribrezhnokletochnoi¼ (littoral cell) angiomy selezenki.

Littoral cell angioma is a very rare benign splenic neoplasm with typical morphological features. It is difficult to differentiate this angioma from other benign or malignant splenic tumors. It is a unique vascular tumor followed by abdominal pain or detected incidentally during examination. Incidence of this tumor is small, as only few appropriate cases were described in the literature. We present successful surgical treatment of littoral cell angioma of the spleen. The issues of clinical course, diagnosis, therapeutic tactics, morphologic and histochemical features are discussed.

Incubation of Lymphocytes with IL-2 Causes the Appearance of Antitumor T Cells Carrying FC, CD25, and LFA-1 on the Surface.

To carry out antitumor activity against cells that have lost surface antigens, human lymphocytes must have a certain repertoire of surface proteins capable of contacting a tumor cell and inducing programmed cell death in it. In this work, we showed that activation of healthy donor cells by IL-2 cytokine within 6 days causes the appearance of FasL, CD25, and LFA-1 proteins on CD8+CD25+ T lymphocytes, and also converts the LFA-1 protein into an active form having a high affinity for its target, ICAM-1 integrin. The appearance of these proteins on the surface of this subpopulation of lymphocytes allows them to induce programmed cell death in HLA-negative tumor cells.

[Main anthropometric indicators of children and adolescents living in the Chuvash Republic in the dynamics of 137 years].

Anthropometric studies conducted in 1884, 1928, 1946, 1965 and 1999 to study the characteristics of growth and weight indicators of children living in the territory of modern Chuvashia, partly reflected the influence of the living conditions of children in certain historical periods of the country's development: revolutions, civil and domestic wars, post-war stabilization, «perestroika¼. Over the last 22-year period, from 1999 to 2021, there has been the largest increase in the growth rate of indicators of the physical development of children and adolescents, which is considered as a positive trend, a manifestation of ongoing acceleration processes. It was revealed that in modern children, physiological growth jumps in comparison with their peers in 1884, 1930, and 1999 occur earlier - in the prepubertal period.

[Expression of HIV-1 Reverse Transcriptase in Murine Cancer Cells Increases Mitochondrial Respiration].

Changes in metabolic pathways are often associated with the development of a wide range of pathologies. Increased glycolysis under conditions of sufficient tissue oxygen supply and its dissociation from the Krebs cycle, known as aerobic glycolysis or the Warburg effect, is a hallmark of many malignant neoplasms. Identification of specific metabolic shifts can characterize the metabolic programming of individual types of tumor cells, the stage of their transformation, and predict their metastatic potential. Viral infection can also alter the metabolism of cells to support the process of viral replication. Infection with human immunodeficiency virus type 1 (HIV-1) is associated with an increased incidence of various cancers, and for some viral proteins a direct oncogenic effect was demonstrated. In particular, we showed that the expression of HIV-1 reverse transcriptase (RT) in 4T1 breast adenocarcinoma cells increases the tumorigenic and metastatic potential of cells in vitro and in vivo by a mechanism associated with the ability of RT to induce reactive oxygen species in cells (ROS). The aim of this work was to study the molecular mechanism of this process, namely the effect of HIV-1 RT on the key metabolic pathways associated with tumor progression: glycolysis and mitochondrial respiration. Expression of HIV-1 RT had no effect on the glycolysis process. At the same time, it led to an increase in mitochondrial respiration and the level of ATP synthesis in the cell, while not affecting the availability of the substrates, carbon donors for the Krebs cycle, which excludes the effect of RT on the metabolic enzymes of cells. Increased mitochondrial respiration was associated with restoration of the mitochondrial network despite the RT-induced reduction in mitochondrial mass. Increased mitochondrial respiration may increase cell motility, which explains their increased tumorigenicity and metastatic potential. These data are important for understanding the pathogenesis of HIV-1 infection, including the stimulation of the formation and spread of HIV-1 associated malignancies.

Tag7-Mts1 Complex Activates Chemotaxis of Regulatory T Cells.

One of the basic features of immune system is the ability to sustain balance between activation and suppression of effector lymphocytes. In this process a key role belongs to the subpopulation of cells called regulatory T cells (Treg). Many cancer and autoimmune diseases are caused by malfunctions of Treg, and investigation of this subpopulation is important for development of new therapeutic approaches. In this study, we demonstrate that regulatory T cells can migrate along the concentration gradient of Tag7-Mts1 complex, and also they produce agents that induce blood cells migration.

[The health of children of adolescent age delivered on time with light and large body mass].

The need to preserve and promote health of children determine one of the basic directions of development of public social policy. It is the most important strategic purpose of modern children health care, since from it depend health of the nation, increasing of life expectancy and national economic potential.Purpose of the study is to assess health status of children of adolescent age born at term with diagnosis "fetus with low birth weight for gestational age" and with large body mass. The bibliographic, information-analytical and comparative analysis methodology were applied.

[Does an attempt to save a limb always prolong the patient's life?] / Vsegda li popytka sokhranit' konechnost' prodlevaet zhizn' patsienta?

AIM: The purpose of the study was to examine overall survival and the incidence of major adverse cardiovascular events, as well as economic expenditures for treatment of patients with occlusion of the femoropopliteal-tibial segment and critical ischaemia in low competence of the outflow channel, with a poor prognosis for endovascular or open revascularization of lower-limb arteries. PATIENTS AND METHODS: We studied the results of treating a total of 68 patients with lower-limb critical ischaemia and low parameters of the outflow channel competence. Primary arterial reconstruction was performed in 48 cases. At various terms after revascularization due to thrombosis of the reconstruction zone and the development of gangrene, amputation of the lower limb was performed: at 3 to 11 (n=25) and at 12 to 24 (n=25) months. Primary amputation of the lower limb was performed in 20 patients. The endpoints of the study included overall survival, the incidence of major adverse cardiovascular events, and economic expenditures for the in-hospital treatment. The average duration of follow-up amounted to 2 years. RESULTS: The obtained findings demonstrated that in patients with lower-limb critical ischaemia and low parameters of the outflow channel competence, redo arterial reconstructions and amputation within 11 months, as well as a high level of surgical risk were associated with a low overall survival rate and the development of major adverse cardiovascular events in the remote period. Secondary surgical interventions on the major vessels significantly increased the cost of treatment.

R482L Mutation of the LMNA Gene Affects Dynamics of C2C12 Myogenic Differentiation and Stimulates Formation of Intramuscular Lipid Droplets.

Mutations in the LMNA gene resulting in the substitution of the highly conserved arginine 482 residue in the globular C-terminal domain of lamin A/C are associated with the Dunnigan-type familial partial lipodystrophy (FPLD2) often accompanied by impairments in the muscle tissue development. The mechanisms underlying these impairments remain unknown. The purpose of our work was to investigate the effects of the LMNA gene mutation R482L on the muscle differentiation and intramuscular fat accumulation using C2C12 mouse myoblasts transduced with the lentiviral constructs carrying the wild-type human LMNA gene (LMNA-WT) or the LMNA-R482L mutant gene. After stimulation of myogenesis and adipogenesis in the transduced cell, expression of muscle and adipose tissue differentiation markers, morphology of differentiated myotubes, and formation of intramuscular lipid droplets were analyzed. C2C12 cells carrying the LMNA-R482L construct exhibited upregulated desmin expression at all stages of muscle differentiation and transformed into hypertrophied myotubules (in comparison with C2C12 myoblasts transduced with LMNA-WT). Reduced expression levels of the myogenic transcription factor Myf6 in the cells with the LMNA-R482L mutant indicated delayed maturation of muscle fibers. These cells more actively accumulated fat in response to the stimulation of adipose differentiation than myoblasts modified with the wild-type LMNA; they also expressed the markers of lipid droplets, such as FABP4 (fatty acid-binding protein 4), ATGL (adipose triglyceride lipase), and PLIN2 (perilipin 2). Therefore, the R482L mutation of the LMNA gene affects the dynamics of C2C12 myoblast differentiation into myotubules and stimulates formation of fat deposits in the myoblasts and myotubules in a tissue-specific manner.

[Spondyloarthritis: modern terminology and definitions].

Aim to identify outdated terms and make changes to the terminology of spondyloarthritis. MATERIALS AND METHODS: At the first stage of the work, the terms divided into two categories: "outdated" definitions and terms that need to be improved or unified. Subsequently, each member of the Expert Group of Spondyloarthritis at the Association of Rheumatologists of Russia (ExSpA) presented by its own definition of the designated term or agreed with the previous term. At the next stage, the existing definitions were put together. After discussion, experts left a term that scored at least 2/3 of the votes. The special opinion of experts was recorded, whose did not coincide with the majority opinion. An open vote was conducted, when defining an "outdated" term with the unanimous decision of all group members, this term was not recommended for further clinical use. RESULTS: The work carried out allowed us to identify a number of terms that are not recommended for use in clinical practice. Number of terms are defined, which should be used when discussing the problem of spondyloarthritis. CONCLUSION: The Expert Group of Spondyloarthritis at the Association of Rheumatologists of Russia suggests using or, accordingly, not using a number of terms and their definitions in clinical practice.

[Outcomes of revascularizing operations on lower-limb arteries in patients with critical ischaemia and multifocal atherosclerosis]. / Iskhody revaskuliariziruiushchikh operatsii na arteriiakh nizhnikh konechnostei u bol'nykh s kriticheskoi ishemiei i mul'tifokal'nym aterosklerozom.

The purpose of this study was to evaluate the amputation-free survival rate and predictors of major adverse cardiovascular events (extracardiac and cardiac mortality, non-fatal myocardial infarction, non-fatal stroke) in patients with atherosclerotic occlusive-stenotic lesions of the femoropopliteal-tibial segment and critical ischaemia. We analysed the results of treating a total of 122 patients with atherosclerotic lesions of the superficial femoral artery and lower limb critical ischaemia. Of these, 35 patients had no lesions of other arterial basins, 24 patients presented with a concomitant lesion of the carotid basin, 41 subjects had lesions of the coronary basin, and 22 had lesions of the coronary and carotid basins. The patients were subjected to either bypass graft operation (n=75) or endovascular intervention (n=47). The evaluated outcome measures were amputation-free survival and the frequency of major adverse cardiovascular events. The average duration of follow up amounted to 38.2±4.3 months. The carried out multivariate logistic regression analysis demonstrated that the factors associated with lower limb amputation and the development of major adverse cardiovascular events were as follows: a concomitant lesion of the coronary (p=0.044) and coronary-carotid (p<0.05) basins, a history of endured myocardial infarction (p=0.003), a C-reactive protein level not less than 17.0 mg/l (p<0.05) and the value of the apolipoprotein B/A1 ratio above 1.0 (p=0.004).

[Leiomyosarcoma of the splenic vein]. / Leiomiosarkoma selezenochnoi veny.

Vascular leiomyosarcoma (LMS) is an extremely rare disease. Venous lesion is approximately 5 times more common than arterial. LMS is usually found in retroperitoneal veins and in inferior vena cava. Lesion of the splenic vein is extremely rare. A 52-year-old woman with recurrent abdominal pain is reported in the article. Abdominal contrast-enhanced CT revealed a 6 cm tumor of the pancreatic tail. The patient underwent laparoscopic distal pancreatectomy with splenectomy en bloc. Histological and immunohistochemical studies revealed LMS originating from the smooth muscles of the splenic vein. Surgery was followed by adjuvant chemotherapy. There was no local recurrence in 1 year after surgery. In this article, we analyze the available information on leiomyosarcoma of the splenic vein.

The association between the development of autoimmune polyglandular syndrome in adults and polymorphism of HLA class II genes and the predisposition to the development of chronic adrenal insufficiency in the context of these syndromes.

AIM: To consider association of chronic adrenal insufficiency in patients with APS of adults with polymorphism of class II HLA genes, -CTLA-4 and PTPN-22. MATERIALS AND METHODS: The case-control study involved 78 patients with APS 2, 3, 4 types and 109 healthy subjects). Alleles of the HLA class II genes, CTLA-4 and PTPN-22 were identified by the multiprimer allele-specific PCR method. The statistical analysis was carried out using the exact two-sided Fisher test. The association of the chronic adrenal insufficiency in patients with APS was determined by the value of the odds ratio (OR - odd's ratio), the value of 95% confidence interval (95% CI - confidence interval). RESULTS: Haplotypes DR3-DQ2 (OR = 4.06), DR4-DQ8 (OR = 5.78), genotype DR3/DR4 (OR = 19.7), DQA1 * 0301 allele (OR = 4.27), as well as genotype DQA1 * 0301 / DQA1 * 0501 (OR = 13.89) predispose to the development of APS of adults compared to the control group. APS patients were divided into two groups according to the presence of chronic adrenal insufficiency (APS 2 and 4 types - in one group and type 3 APS in the other group). Haplotype DR3-DQ2 (DRB1 * 17-DQA1 * 0501 -DQB1 * 0201) (OR = 2.6), as well as the genotype DR3/DR4 (OR = 4.28) found the strongest association with the development of adrenal insufficiency in patients with APS of adults. Protective haplotypes DRB1 * 01-DQA1 * 0101-DQB1 * 0501 (p<0.01, OR = 0.07), as well as the DRB1 * 01 allele (p<0.01, OR = 0.08) have been identified with respect to the development of adrenal insufficiency in adult APS patients. CONCLUSION: Examination of patients with APS of adults without chronic adrenal insufficiency for the presence of protective genes for the development of adrenal insufficiency will allow better predicting the risks of developing of the disease within the syndrome.

Factors affecting the results of analgesic therapy. Results of the Russian multicentre study of NOTE (NSAID: Open-label Trial of Efficacy).

AIM: To identify factors affecting the effectiveness of NSAIDs in patients with OA and LBP. MATERIALS AND METHODS: An observational study was conducted to evaluate the effectiveness of a 2-week course of NSAIDs in OA and LBP in real clinical practice. The study group consisted of 3604 patients with OA and LBP (60.6% women and 39.4% men, mean age 55.0±13.4 years). According to the study design, aceclofenac (Airtal) and other NSAIDs used in the ratio 1:1. The main criterion of effectiveness was the frequency of complete pain relief after 2 weeks of therapy. In addition, the decrease of pain and general health were determined on a 10-point numerical rating scale (NRS). We compared the frequency of complete pain relief in patients who had and did not have the studied factors. The value of the studied factors was determined using OR (95% CI). RESULTS: Most patients received aceclofenac (54.9%), as well as diclofenac (2.0%), ketoprofen (1.9%), lornoxicam (2.2%), meloxicam (13.7%), naproxen (2.1%), nimesulide (5.8%), celecoxib (5.9%), ethicoxib (7.1%) and other NSAIDs (4.4%); 56.2% of patients received muscle relaxants, mainly tolperisone (74.7%), vitamin B (10.4%), and proton pump inhibitors (42.8%). Complete pain relief was achieved in 54.8% of patients. The pain decrease and general health improvement were (for NRS) 63.9±13.4% and 61.7±14.8%, respectively. The efficacy of aceclofenac was slightly higher than in the whole group: complete pain relief was in 59.9% of patients. Adverse events in aceclofenac use were observed in 2.3% of patients, other NSAIDs-from 2.4 to 14.1%. The frequency of complete pain relief was higher in men: OR 1,239 (95% CI 1.08-1.418; p=0.002), who had the first episode of pain - OR 3.341 (95% CI 2.873-3.875; p=0.000), a good" response " to NSAIDs in history - OR 1.656 (95% CI 1.385-1.980; p=0.000) and received NSAIDs in combination with muscle relaxants - OR 1.218 (95% CI 1.067-1.390; p=0.004). The effect of therapy is lower in patients 65 years and older-OR 0,378 (95% CI 0.324-0.442; p=0,000), with body mass index >30 kg/m² - OR 0.619 (95% CI 0.529-0.723; p=0.000), with severe pain (≥7 points NRS) - OR 0.662 (95% CI 0.580-0.756; p=0.002), with pain at rest, - OR 0.515 (95% CI 0.450-0,589; p=0.000), pain at night - OR 0.581 (95% CI 0.501-0.672; p=0.000) and the presence of stiffness - OR 0.501 (95% CI 0.438-0,573; p=0.000). Treatment results are significantly worse in the cases of combination of LBP and joint pain, as well as pain in the trochanter major and pes anserinus area (p<0.001). CONCLUSION: NSAIDs are the first-line medications for the pain treatment in LBP and OA. Aceclofenac is effective and safe in this conditions. When carrying out analgesic therapy should take into account factors that affect the effectiveness of treatment: old age, overweight, insufficient effect of NSAIDs in history, severe pain, signs of "inflammatory" pain, multiple sources of pain.

Polymer dynamics under cylindrical confinement featuring a locally repulsive surface: A quasielastic neutron scattering study.

We investigated the effect of intermediate cylindrical confinement with locally repulsive walls on the segmental and entanglement dynamics of a polymer melt by quasielastic neutron scattering. As a reference, the corresponding polymer melt was measured under identical conditions. The locally repulsive confinement was realized by hydrophilic anodic alumina nanopores with a diameter of 20 nm. The end-to-end distance of the hydrophobic infiltrated polyethylene-alt-propylene was close to this diameter. In the case of hard wall repulsion with negligible local attraction, several simulations predicted an acceleration of segmental dynamics close to the wall. Other than in attractive or neutral systems, where the segmental dynamics is slowed down, we found that the segmental dynamics in the nanopores is identical to the local mobility in the bulk. Even under very careful scrutiny, we could not find any acceleration of the surface-near segmental motion. On the larger time scale, the neutron spin-echo experiment showed that the Rouse relaxation was not altered by confinement effects. Also the entanglement dynamics was not affected. Thus at moderate confinement conditions, facilitated by locally repulsive walls, the dynamics remains as in the bulk melt, a result that is not so clear from simulations.

Experimental Study of the Effects of Nanodispersed Ceria on Wound Repair.

We studied the effects of nanodispersed ceria on wound healing in vitro and in vivo. It was found that cerium dioxide stimulated wound healing, which manifested in shrinkage of burn wound area (by 1.5 times) and intensification (by 2.4 times) marginal epithelialization.

[Allergic rhinitis among the children of the Republic of Sakha (Yakutiya)]. / Allergicheskii rinit u detei Respubliki Sakha (Iakutiia).

The objective of the present study was to elucidate dynamics of primary allergic rhinitis (AR) morbidity in the children population of the Republic of Sakha (Yakutiya) from the statistical materials of the Yakutian Republican Information and Analytical Centre available for the period from 2008 to 2014 in the combination with the results of allergological testing based at the National Centre of Medicine, Yakutsk, that involved 100 schoolchildren presenting with allergic rhinitis who resided in the northern regions of the Republic. The results of the study give evidence of the increasing primary allergic rhinitis morbidity rate among the population of the children and adolescents during the recent years. It is concluded that the regional programs for the prevention and early diagnostics of primary allergic rhinitis need to be elaborated and introduced in the practical work of healthcare facilities over the territory of the Republic.

[The effect of controllable moderate hypothermia on hemostasis in newborns with hypoxemic ischemic encephalopathy.]

THE PURPOSE: To study effect of controllable moderate hypothermia on system of hemostasis in newborns with hypoxemic ischemic encephalopathy. MATERIALS AND METHODS: The retrospective analysis was carried out concerning 38 medical records of newborns with acute hypoxia of fetus (group I), 12 medical records of newborns with acute hypoxia of fetus against the background of chronic hypoxia of fetus (group II), 20 healthy newborns (group III) and 20 healthy adults. The thromboelastography was implemented in three stages: at first, third and sixth days of life of newborns. CONCLUSION: The thromboelastography is to be implemented in newborns with hypoxemic ischemic encephalopathy due to occurrence of of hemostasis shifting to hypocoagulation and high risk of bleeding. In healthy full-term children a physiological hypercoagulation was established as compared with adults without alterations of processes of lysis of clots. In newborns with chronic hypoxia of fetus against the background of applied medical hypothermia, in comparison with healthy newborns, decreasing of number of thrombocytes are observed and possibly lower functional activity of thrombocytes up to third day and also lower activity of plasma component of hemostasis at retained elasticity and strength of developed clots. The sixth day, after heating, the system of hemostasis is normalized and number of thrombocytes is restored. In newborns, having acute hypoxia of fetus against the background of chronic hypoxia of fetus higher risk of bleeding is noted at minimal difference according results of thromboelastography.

Polymer loaded microemulsions: Changeover from finite size effects to interfacial interactions.

Form fluctuations of microemulsion droplets are observed in experiments using dielectric spectroscopy (DS) and neutron spin echo spectroscopy (NSE). Previous work on dioctyl sodium sulfosuccinate based water in oil microemulsions in the droplet phase has shown that adding a water soluble polymer (Polyethylene glycol M = 1500 g mol-1) modifies these fluctuations. While for small droplet sizes (water core radius rc < 37 Å) compared to the size of the polymer both methods consistently showed a reduction in the bending modulus of the surfactant shell as a result of polymer addition, dielectric spectroscopy suggests the opposite behaviour for large droplets. This observation is now confirmed by NSE experiments on large droplets. Structural changes due to polymer addition are qualitatively independent of droplet size. Dynamical properties, however, display a clear variation with the number of polymer chains per droplet, leading to the observed changes in the bending modulus. Furthermore, the contribution of structural and dynamical properties on the changes in bending modulus shifts in weight. With increasing droplet size, we initially find dominating finite size effects and a changeover to a system, where interactions between the confined polymer and the surfactant shell dominate the bending modulus.

Mediators and Biomarkers of Inflammation in Meningitis: Cytokine and Peptidome Profiling of Cerebrospinal Fluid.

Differential diagnosis of bacterial and viral meningitis is an urgent problem of the modern clinical medicine. Early and accurate detection of meningitis etiology largely determines the strategy of its treatment and significantly increases the likelihood of a favorable outcome for the patient. In the present work, we analyzed the peptidome and cytokine profiles of cerebrospinal fluid (CSF) of 17 patients with meningitis of bacterial and viral etiology and of 20 neurologically healthy controls. In addition to the identified peptides (potential biomarkers), we found significant differences in the cytokine status of the CSF of the patients. We found that cut-off of 100 pg/ml of IL-1ß, TNF, and GM-CSF levels discriminates bacterial and viral meningitis with 100% specificity and selectivity. We demonstrated for the first time the reduction in the level of two cytokines, IL-13 and GM-CSF, in the CSF of patients with viral meningitis in comparison with the controls. The decrease in GM-CSF level in the CSF of patients with viral meningitis can be explained by a disproportionate increase in the levels of cytokines IL-10, IFN-γ, and IL-4, which inhibit the GM-CSF expression, whereas IL-1, IL-6, and TNF activate it. These observations suggest an additional approach for differential diagnosis of bacterial and viral meningitis based on the normalized ratio IL-10/IL-1ß and IL-10/TNF > 1, as well as on the ratio IFN-γ/IL-1ß and IFN-γ/TNF < 0.1. Our findings extend the panel of promising clinical and diagnostic biomarkers of viral and bacterial meningitis and reveal opposite changes in the cytokine expression in meningitis due to compensatory action of pro- and antiinflammatory factors.